IFI16 acts as a nuclear pathogen sensor to induce the inflammasome in response to Kaposi sarcoma associated herpesvirus infection

By N. Kerur, M. Veettil, N. Sharma-Walia, V. Bottero, Sathish Sadagopan, P. Otageri, B. Chandran. Cell Host and Microbe, 2011

708 citations recorded by the source corpus.

SUMMARY Inflammasomes are cytoplasmic sensors of foreign molecules, including pathogens, and function to induce caspase-1 activation and IL-1β cytokine maturation. Whether such a mechanism exists in the nucleus and is effective against nuclear replicating pathogens is unknown. Nuclear replicating herpesvirus KSHV is associated with Kaposi Sarcoma, an angioproliferative tumor characterized by an inflammatory microenvironment including IL-1β. We demonstrate that during KSHV infection of endothelial cells, interferon gamma-inducible protein 16 (IFI16) interacts with the adaptor molecule ASC and procaspase-1 to form a functional inflammasome. This complex was initially detected in the nucleus and subsequently in the peri-nuclear area. KSHV gene expression and/or latent KSHV genome is required for inflammasome activation and IFI16 colocalizes with the KSHV genome in the infected cell nucleus. Caspase-1 activation by KSHV was reduced by IFI16 and ASC silencing. Our studies reveal IFI16 as a nuclear pathogen sensor and demonstrate that the inflammasome also functions in the nucleus.

Subfields: Immunology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/e316cbee4afb43eaf7038b70df241b69cc9caefd

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Citations in the corpus

Regulation of inflammasome activation (2015, background): “IFI16 initiates inflammasome activities in response to Kaposi sarcoma-associated herpesvirus (212), Epstein–Barr virus (213), and herpes simplex virus-1 (HSV-1) (214).”
Inflammation and its role in age-related macular degeneration (2016, background): “IFI16 is also a DNA sensor capable of assembling inflammasomes but it seems to specialize in searching for nuclear intruders, whereas AIM2 detects foreign DNA in the cytoplasm [54, 56, 57, 60, 61].”
Pattern Recognition Receptors and the Innate Immune Response to Viral Infection (2011, background): “recognition of nuclear DNA during infection with this virus [59].”
Pyroptotic cell death defends against intracellular pathogens (2015, background): “IFI16 is a human ALR that detects viral dsDNA in the nucleus and activates caspase-1 (58).”
Cytosolic Sensing of Viruses (2013, background): “Although there is also a suggestion that DNA sensing might additionally occur in the nucleus (Kerur et al., 2011; Li et al., 2012), efforts have focused on identifying the pathways that mediate the sensing of DNA in the cell cytosol and link it to inflammation (Figure 4).”
The cell biology of inflammasomes: Mechanisms of inflammasome activation and regulation (2016, background): “The AIM2 inflammasome is also inhibited by host-encoded decoy molecules and dominant-negative regulators (Dombrowski et al., 2011; Morizane et al., 2012; Khare et al., 2014).”
Innate Immune Pattern Recognition: A Cell Biological Perspective (2015, neutral): “A more diverse set of functions has been attributed to a second member, IFI16, including the activation of STINGdependent IFN production and inflammasome formation (231, 247).”